Peripheral Neuropathy in Children and Adolescents with Insulin-dependent Diabetes Mellitus

Objective Type 1 diabetes mellitus (T1DM) is a chronic immune-mediated disease. Diabetic peripheral neuropathy (DPN) is an important microvascular complication of T1DM. One of the most important risk factors for the development of DPN is poor glycemic control. We evaluated the prevalence of DPN among T1DM patients and determined the association between DPN and glycated hemoglobin (HbA1c) level. Materials & Methods The subjects were recruited prospectively upon initial evaluation at Imam Reza Hospital, Mashhad, Iran from Jan 2013 to Jan 2015. Patients with T1DM were selected based on the inclusion criteria (i.e., age of 6≤yr and absence of other co-morbidities). DPN was assessed through electrodiagnostic studies and neurological examinations, while diabetes control was evaluated by measuring the HbA1c level. Results Fifty patients with T1DM were enrolled in this study. The mean diabetes duration of patients was 8.38±3.79 yr (mean age16.68±6.68 yr). The mean HbA1c level was 8.6±2.1% in patients without DPN and 10.5±3 in those with DPN (P=0.016). Overall, 24% of the subjects were presented with DPN according to nerve conduction velocity study (NCV) findings. A positive correlation was found between NCV and clinical symptoms with signs (P<0.001, r=0.45 and P<0.001, r=0.644, respectively). Sensitivity and specificity of neurological examination for DPN diagnosis were 91.7% and 63.2%, respectively. Poor diabetes control is associated with DPN. Moreover, HbA1c level was used as an index for glycemic control over the past 3 months. Conclusion Rigid blood glucose control and periodic neurological examinations were the best strategies to prevent DPN.


Introduction
Type 1 diabetes mellitus (T1DM) is a chronic immune-mediated disease, in which the pancreas ceases to produce enough insulin (1). The overall increase in the incidence of T1DM was estimated at nearly 3%, and the annual incidence of this condition varied from 0.61 cases per 100000 populations in China to 57.6 cases per 100000 in Finland (2,3). Middle East region, Saudi Arabia and Kuwait have the highest incidence rate at 31.4 and 22.3/100000 per year (4).
Annually, 1 to 35 new cases of T1DM (younger than 14 yr) per 100000 populations are diagnosed per year. In various countries, the incidence rate of T1DM has at least doubled over the past two decades.
The incidence of this condition seems to raise as the distance from the equator increases (5, 6).
Peripheral nervous system involvement is a common complication of T1DM, and unlike adults, patient's polyneuropathy has no clinical manifestations in diabetic children (7). The prevalence of neuropathy varies depending on the severity and duration of hyperglycemia (1). The prevalence of peripheral neuropathy in both adults and children ranges between 7% and 57% (8).
Nerve conduction velocity (NCV) test is the method of choice for the diagnosis of neuropathy.

The incidence of neuropathy in different studies
ranges from 10% to 68% among diabetic patients (9,10).
In this study, we evaluated the sign and symptoms of peripheral polyneuropathy and its correlation with glycated hemoglobin (HbA1c) level as an indicator of metabolic control in diabetic patients in Mashhad City, Eastern Iran.

Materials & Methods
The subjects were recruited prospectively upon initial  NCV and distal latency tests were performed in the following nerves: Common peroneal nerve, tibial nerve, superficial peroneal nerve, and sural (sensory) nerve in the lower extremities, as well as median (motor and sensory) nerves in the upper extremities, were observed in the tests. Electrodiagnostic studies were conducted by one single operator and device (Myto, Italy). We evaluated 50 diabetic patients, divided into two groups: group A with abnormal NCV, and group B with normal NCV.
Normality of variables was tested by Kolmogorov-Smirnov test. Then, parametric or non-parametric tests were performed to determine the difference and relationship between variables. For data analysis, SPSS Ver. 16 (Chicago, IL, USA) was applied, and the collected data with referral codes were imported into the software. P-value less than 0.05 were considered statistically significant.

Results
FiftyT1DM patients with the mean age of 16.68±6.98 yr and disease duration of 8.36±3.79 yr were enrolled (Table 1). Overall, 54% (n=27) of the participants were female. Twenty one (42%) patients were clinically asymptomatic, while 29 (58%) cases had at least one of the signs or symptoms of peripheral neuropathy. Abnormal pain sensation was detected in 9 (18%) patients, and the frequency of paresthesia, numbness, and burning sensation was 6%, 28%, and 8%, respectively; in total, and 30 (60%) patients had one abnormal symptom. Neurological examination was suggestive of impaired temperature sensation in 6 (12%) cases. Reduced vibration perception, abnormal Achilles reflex, and impaired touch perception were reported in 5 (10%), 15 (30%), and 3 (6%) cases, respectively; overall, 29 (58%) patients had one abnormal sign. Abnormal Achilles reflex and numbness were the most common findings in our study population (Table 2).
Moreover, subclinical DPN was reported in up to 60% of patients in Isfahan, Iran (12). Various studies have introduced diabetes duration as a major factor in DPN development (11,(13)(14)(15)(16), although this finding has not been confirmed in other studies (17,18), similar to the present research. On the other hand, diabetic neuropathy and abnormal NCV findings have been reported in patients with recently diagnosed diabetes by some researchers (14,19).
Patients with diabetic neuropathy have few complaints, and their physical examination may reveal variable degrees of sensory loss (20). In our study, 28% of all subjects experienced numbness and 30% showed abnormal tendon reflex. Reduction in pain perception on neurological examinations, abnormal tendon reflex, and numbness were more significant in-group A, compared to group B. The frequency of abnormal pain sensation, paresthesia, and burning sensation was estimated at 18%, 6%, and 8%, respectively. Neurological examination was suggestive of impaired temperature sensation, reduced pain perception, reduced vibration perception, abnormal tendon reflex, and impaired touch perception in 12%, 0%, 10%, 30%, and 6% of subjects, respectively.
The present findings revealed a positive correlation between clinical symptoms and abnormal NCV with sensitivity of 91.7% and specificity of 84.2% (Table 3). Therefore, serial neurological examinations could be used for the diagnosis of diabetic neuropathy in clinics. Deep peroneal and sural nerves were the most commonly affected nerves in our patients (18); moreover, in two patients, the mentioned diagnosis associated with carpal tunnel syndrome was detected.  (25).
In fact, in the present study, diabetic neuropathy had no positive correlation with age, sex, BMI, duration of disease, or hyperlipidemia, whereas a significant correlation between HbA1c level and diabetic neuropathy was observed.
In conclusion, the best strategy to prevent diabetic neuropathy is rigid blood glucose control and periodic neurological examinations and the poor glycemic control is a determining factor in peripheral neuropathy in type 1 diabetic patients.

Acknowledgment
We thank the Vice Chancellor for Research